Abstract

The central nervous system (CNS) is a common site of disease progression in patients with non-small-cell lung cancer (NSCLC) with anaplastic lymphoma kinase (ALK)-rearrangement treated with crizotinib. Cystic brain metastases (CBM) have been recently identified as one possible variant of this disease. An illustrative case report is presented along with a literature review performed in order to track relevant papers about CBM in ALK-rearranged NSCLC, including possible pathophysiology, differential diagnosis and treatment options for this condition. Three case reports have been published describing six ALK-rearranged NSCLC patients presenting with CBM, all of which were under treatment with crizotinib by the time of CBM diagnosis. Treatment with CNS-penetrating tyrosine kinase inhibitors (TKIs) resulted in CNS disease control in three of the six cases reported either as single therapy or in combination with radiation therapy (RT). Investigation of differential diagnoses of CBM might be necessary, which include inflammatory and demyelinating disorders, primary brain tumours and infectious diseases, especially neurocysticercosis that might mimic CBM images. Treatment options include RT, CNS-penetrating TKIs and invasive procedures, such as stereotactic drainage. Thus, CBM are associated with ALK-rearranged NSCLC, particularly in patients who use crizotinib and should prompt investigation of differential diagnosis. CNS-penetrating TKIs are effective in the control of solid brain metastases and also seem to be active in CBM as single therapy or in combination with RT.

Highlights

  • A chromosomal inversion leading to the fusion of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene was identified in 2007 [1], resulting in the EML4-ALK fusion protein, a therapeutic target in advanced non-smallcell lung cancer (NSCLC)

  • Three case reports have been published describing six ALK-rearranged NSCLC patients presenting with Cystic brain metastases (CBM) [14,15,16], all of which were under treatment with crizotinib by the time of CBM diagnosis

  • Based on the present and on the previous case reports, we conclude that ALK-rearranged NSCLC is associated with CBM, in patients in use of crizotinib

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Summary

Introduction

A chromosomal inversion leading to the fusion of the anaplastic lymphoma kinase (ALK) gene with the echinoderm microtubule-associated protein-like 4 (EML4) gene was identified in 2007 [1], resulting in the EML4-ALK fusion protein, a therapeutic target in advanced non-smallcell lung cancer (NSCLC). Patients with EML4-ALK fusion and other ALK rearrangements represent 3–7% of all NSCLC cases, usually associated with younger age, never smoking or light smoking history and adenocarcinoma histology (especially in those tumours harbouring signet-ring cell features) [1, 2]. This subset of patients is responsive to the ALK inhibitor crizotinib, with an objective response rate of approximately 60% and a median progression-free survival (PFS) of 8–10 months [3, 4]. We report a case of CBM in ALK-rearranged NSCLC and a literature review

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